Obtained for the unplatinated oligomer reveals a

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obtained for the unplatinated oligomer, reveals a difference in the midpoint of the transition in chemical shift of the H8 proton by ~ 2 pH units if coordination occurs at N7. This effect is illustrated in Figure 9. 19 for the adduct cis- [Pt(NH 3 h{d(ApGpGpCpCpT)}N7-G(2),N7-G(3)], where the pK a of Nl is seen to shift from ~ 10 to ~ 8 upon platination. 71 The pH titration in this example also reveals the pH-dependent chemical shift of the cytosine 1 H resonances at a pH of ~ 4.5, corresponding to protonation of the N3 atoms. The protonation of adenine N7 (pK a ~ 4) is also frequently observed in these studies. These results conclusively demonstrate platinum coordination at N7 of the two guanosine nu- cleosides. Although several of the oligonucleotides studied have self-complementary sequences, such that they can form a double helix when unplatinated, in no such case was a duplex observed for their platinated forms. The presence of the platinum-induced crosslink presumably decreases the stability of the double- stranded form of the oligonucleotide. Another interesting result is that all intra- strand {Pt(NH 3 hP+ adducts of d(GpG) or d(ApG) have an altered deoxyribose- sugar ring conformation. In normal, unplatinated form, these single-stranded or duplex oligonucleotides have a C2'-endo sugar pucker (Figure 9.9). Upon plat- ination, the 5' -nucleotide switches to C3'-endo. This change is readily moni- tored by the ring proton-coupling constants J HI '-H2' and J HI '-H2". These protons constitute an ABX spin system such that the sum, 2:,3J = 3J 1 '2' + 3J 1 '2'" is most easily measured as the separation between the outermost peaks in the mul- tiplet. For the C2'-endo conformation, a pseudotriplet occurs with 2:,3J = 13.6 Hz, and for C3'-endo, 2:,3J = 7.5 Hz. The 3'-guanosines in the adducts show greater conformational flexibility, having ~ 70 to 80 percent C2'-endo sugar puckers, depending upon the temperature. Another conformational feature that could be deduced from 1 H NMR studies of all cis-DDP-platinated oligonucleotides containing an embedded d(GpG) se- quence is that both guanosine nucleosides retain the anti orientation of the base around the Cl'-N9 glycosidic linkage (Figure 9.9). This result was deduced from the lack of a pronounced nuclear Overhauser effect (NOE) between H8 and the HI' protons, such as would occur in the syn conformation. An NOE between H8 resonances on the two coordinated nucleosides was observed for
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Figure 9.19 Chemical shift (0) vs. pH* of the nonexchangeable base protons of D 2 0 solutions of [d(ApGpGpCpCpT)h (3.5 mM, 35°C) and its cis-DDP adduct (2.5 mM, 70°C). The pyrimi- dine resonances of the latter sample show no chemical shift changes with temperature over the range 35 < T < 70°C while the purine resonances show a slight temper- ature-dependent chemical shift change of up to 0.1 ppm. Tetra- methylammonium chloride was used as the internal standard (0 3.180). Reproduced by permission from J.
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